LOCAL AND SYSTEMIC FACTORS IN PERIODONTAL-DISEASE INCREASE MATRIX-DEGRADING ENZYME-ACTIVITIES IN RAT GINGIVA - EFFECT OF MICOCYCLINE THERAPY

We previously reported that both local and systemic factors relevant t o the pathogenesis of periodontal disease can increase gingival collag enase activity in rats. Since the degradation of extracellular matrix is an essential feature of periodontal disease and this tissue breakdo wn requires multiple enzyme interactions, the current study was carrie d out to determine the effects of bacterial endotoxin (LPS) (a local f actor) and diabetes (a systemic factor) on a panel of matrix-degrading enzymes (collagenase, gelatinase, elastase, and beta-glucuronidase) i n the gingiva of rats. In addition, the effects of therapy with a semi synthetic tetracycline (minocycline) were investigated. Ten male, Spra gue-Dawley rats were made diabetic by IV injection of streptozotocin, Four of the ten rats then received minocycline (10 mg/day) by oral gav age on a daily basis for 3 weeks. Nineteen nondiabetic rats served as controls and 9 of them received 10 mu l of E. coil LPS (10 mg/ml) by i njection into the labial gingiva every other day during the last week of the study. The other 10 nondiabetic rats were sham injected with sa line into the gingiva At the end of the 3 week experimental period, gi ngival tissue and skin were dissected from each rat and extracted for enzyme analysis. Our results showed that diabetes markedly increased t he four matrix-degrading enzyme activities in both gingiva and skin. I n contrast, local LPS injection increased these enzyme activities in t he gingiva alone. Systemic therapy with minocycline completely amelior ated these elevated enzyme levels in diabetic rats in both gingiva and skin. Minocycline added in vitro to the enzyme assay systems containi ng skin extract from diabetic rats also inhibited collagenase and gela tinase activities, but no inhibition was observed for elastase and B-g lucuronidase activities, indicating that the MMPs and other enzymes we re inhibited by minocycline, during diabetes, by indirect and indirect mechanisms, respectively.